NL8800099A - Pilocarpinederivaten en werkwijzen voor het bereiden en toepassen van deze derivaten. - Google Patents
Pilocarpinederivaten en werkwijzen voor het bereiden en toepassen van deze derivaten. Download PDFInfo
- Publication number
- NL8800099A NL8800099A NL8800099A NL8800099A NL8800099A NL 8800099 A NL8800099 A NL 8800099A NL 8800099 A NL8800099 A NL 8800099A NL 8800099 A NL8800099 A NL 8800099A NL 8800099 A NL8800099 A NL 8800099A
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- NL
- Netherlands
- Prior art keywords
- compounds
- methyl
- formula
- acid addition
- carbon atoms
- Prior art date
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- 238000000034 method Methods 0.000 title claims description 13
- QCHFTSOMWOSFHM-WPRPVWTQSA-N (+)-Pilocarpine Chemical class C1OC(=O)[C@@H](CC)[C@H]1CC1=CN=CN1C QCHFTSOMWOSFHM-WPRPVWTQSA-N 0.000 title description 6
- 150000001875 compounds Chemical class 0.000 claims description 60
- 150000003839 salts Chemical class 0.000 claims description 17
- 239000002253 acid Substances 0.000 claims description 16
- 125000004432 carbon atom Chemical group C* 0.000 claims description 13
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 12
- -1 carbamoyloxy group Chemical group 0.000 claims description 11
- 125000000217 alkyl group Chemical group 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 208000024827 Alzheimer disease Diseases 0.000 claims description 4
- VKCLPVFDVVKEKU-UHFFFAOYSA-N S=[P] Chemical compound S=[P] VKCLPVFDVVKEKU-UHFFFAOYSA-N 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 3
- 208000010412 Glaucoma Diseases 0.000 claims description 2
- 206010026749 Mania Diseases 0.000 claims description 2
- 206010039966 Senile dementia Diseases 0.000 claims description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 2
- 208000020016 psychiatric disease Diseases 0.000 claims description 2
- 201000000980 schizophrenia Diseases 0.000 claims description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 2
- 239000012458 free base Substances 0.000 claims 3
- JXAJWBRCZUTMII-UHFFFAOYSA-N 3-methyl-3h-thiophen-2-one Chemical compound CC1C=CSC1=O JXAJWBRCZUTMII-UHFFFAOYSA-N 0.000 claims 1
- 206010028372 Muscular weakness Diseases 0.000 claims 1
- 239000002585 base Substances 0.000 claims 1
- 150000002391 heterocyclic compounds Chemical class 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 42
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- 239000000203 mixture Substances 0.000 description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 230000001713 cholinergic effect Effects 0.000 description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 229960004373 acetylcholine Drugs 0.000 description 6
- 239000000155 melt Substances 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 230000003518 presynaptic effect Effects 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 5
- 229910021529 ammonia Inorganic materials 0.000 description 5
- 239000003480 eluent Substances 0.000 description 5
- 230000001242 postsynaptic effect Effects 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 239000000472 muscarinic agonist Substances 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 229940121948 Muscarinic receptor antagonist Drugs 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- QCHFTSOMWOSFHM-UHFFFAOYSA-N SJ000285536 Natural products C1OC(=O)C(CC)C1CC1=CN=CN1C QCHFTSOMWOSFHM-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 210000001320 hippocampus Anatomy 0.000 description 3
- 239000003149 muscarinic antagonist Substances 0.000 description 3
- 210000001640 nerve ending Anatomy 0.000 description 3
- 229960001416 pilocarpine Drugs 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- 229910052717 sulfur Inorganic materials 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- HIAWOOPBUBXZSZ-UHFFFAOYSA-N 1-sulfanylidene-2,3-dihydrothiophene Chemical compound S=S1CCC=C1 HIAWOOPBUBXZSZ-UHFFFAOYSA-N 0.000 description 2
- NKAMYGXYCWMPTC-UHFFFAOYSA-N 3h-thiophen-2-one Chemical compound O=C1CC=CS1 NKAMYGXYCWMPTC-UHFFFAOYSA-N 0.000 description 2
- 229930000680 A04AD01 - Scopolamine Natural products 0.000 description 2
- 208000003098 Ganglion Cysts Diseases 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- STECJAGHUSJQJN-GAUPFVANSA-N Hyoscine Natural products C1([C@H](CO)C(=O)OC2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-GAUPFVANSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- STECJAGHUSJQJN-UHFFFAOYSA-N N-Methyl-scopolamin Natural products C1C(C2C3O2)N(C)C3CC1OC(=O)C(CO)C1=CC=CC=C1 STECJAGHUSJQJN-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- 208000005400 Synovial Cyst Diseases 0.000 description 2
- 239000011149 active material Substances 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 239000012300 argon atmosphere Substances 0.000 description 2
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 230000002964 excitative effect Effects 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-M fumarate(1-) Chemical compound OC(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-M 0.000 description 2
- 230000000971 hippocampal effect Effects 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 description 2
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- 230000003551 muscarinic effect Effects 0.000 description 2
- 210000001577 neostriatum Anatomy 0.000 description 2
- MUBZPKHOEPUJKR-UHFFFAOYSA-M oxalate(1-) Chemical compound OC(=O)C([O-])=O MUBZPKHOEPUJKR-UHFFFAOYSA-M 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- KOUKXHPPRFNWPP-UHFFFAOYSA-N pyrazine-2,5-dicarboxylic acid;hydrate Chemical compound O.OC(=O)C1=CN=C(C(O)=O)C=N1 KOUKXHPPRFNWPP-UHFFFAOYSA-N 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- STECJAGHUSJQJN-FWXGHANASA-N scopolamine Chemical compound C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-FWXGHANASA-N 0.000 description 2
- 229960002646 scopolamine Drugs 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 239000008096 xylene Substances 0.000 description 2
- JWLXVZOTMXQDFY-UHFFFAOYSA-N 2,3-dihydroxy-2-(2-methylphenyl)butanedioic acid Chemical class CC1=CC=CC=C1C(O)(C(O)C(O)=O)C(O)=O JWLXVZOTMXQDFY-UHFFFAOYSA-N 0.000 description 1
- BHKAWXZKFKVZLK-UHFFFAOYSA-N 2,3-ditert-butyl-6-methylphenol Chemical compound CC1=CC=C(C(C)(C)C)C(C(C)(C)C)=C1O BHKAWXZKFKVZLK-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 229940100578 Acetylcholinesterase inhibitor Drugs 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- YIIMEMSDCNDGTB-UHFFFAOYSA-N Dimethylcarbamoyl chloride Chemical compound CN(C)C(Cl)=O YIIMEMSDCNDGTB-UHFFFAOYSA-N 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- UQOFGTXDASPNLL-XHNCKOQMSA-N Muscarine Chemical compound C[C@@H]1O[C@H](C[N+](C)(C)C)C[C@H]1O UQOFGTXDASPNLL-XHNCKOQMSA-N 0.000 description 1
- 102000014415 Muscarinic acetylcholine receptor Human genes 0.000 description 1
- 108050003473 Muscarinic acetylcholine receptor Proteins 0.000 description 1
- 102000004108 Neurotransmitter Receptors Human genes 0.000 description 1
- 108090000590 Neurotransmitter Receptors Proteins 0.000 description 1
- RSDOPYMFZBJHRL-UHFFFAOYSA-N Oxotremorine Chemical compound O=C1CCCN1CC#CCN1CCCC1 RSDOPYMFZBJHRL-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- PIJVFDBKTWXHHD-UHFFFAOYSA-N Physostigmine Natural products C12=CC(OC(=O)NC)=CC=C2N(C)C2C1(C)CCN2C PIJVFDBKTWXHHD-UHFFFAOYSA-N 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 1
- RSWGJHLUYNHPMX-ONCXSQPRSA-N abietic acid Chemical compound C([C@@H]12)CC(C(C)C)=CC1=CC[C@@H]1[C@]2(C)CCC[C@@]1(C)C(O)=O RSWGJHLUYNHPMX-ONCXSQPRSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 125000005115 alkyl carbamoyl group Chemical group 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 238000003501 co-culture Methods 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 210000003405 ileum Anatomy 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 230000028161 membrane depolarization Effects 0.000 description 1
- 230000006386 memory function Effects 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 206010028417 myasthenia gravis Diseases 0.000 description 1
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 239000004031 partial agonist Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229960001697 physostigmine Drugs 0.000 description 1
- PIJVFDBKTWXHHD-HIFRSBDPSA-N physostigmine Chemical compound C12=CC(OC(=O)NC)=CC=C2N(C)[C@@H]2[C@@]1(C)CCN2C PIJVFDBKTWXHHD-HIFRSBDPSA-N 0.000 description 1
- RNAICSBVACLLGM-GNAZCLTHSA-N pilocarpine hydrochloride Chemical compound Cl.C1OC(=O)[C@@H](CC)[C@H]1CC1=CN=CN1C RNAICSBVACLLGM-GNAZCLTHSA-N 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 210000002763 pyramidal cell Anatomy 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006277 sulfonation reaction Methods 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Ophthalmology & Optometry (AREA)
- Psychiatry (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Hydrogenated Pyridines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE3702940 | 1987-01-31 | ||
| DE3702940 | 1987-01-31 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NL8800099A true NL8800099A (nl) | 1988-08-16 |
Family
ID=6319976
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NL8800099A NL8800099A (nl) | 1987-01-31 | 1988-01-18 | Pilocarpinederivaten en werkwijzen voor het bereiden en toepassen van deze derivaten. |
Country Status (27)
| Country | Link |
|---|---|
| US (1) | US4835174A (enExample) |
| JP (1) | JPS63201185A (enExample) |
| KR (1) | KR880009013A (enExample) |
| AT (1) | AT395852B (enExample) |
| AU (1) | AU607966B2 (enExample) |
| BE (1) | BE1001005A3 (enExample) |
| CA (1) | CA1327805C (enExample) |
| CH (1) | CH675721A5 (enExample) |
| CS (1) | CS411291A3 (enExample) |
| DK (1) | DK46288A (enExample) |
| ES (1) | ES2008421A6 (enExample) |
| FI (1) | FI90080C (enExample) |
| FR (1) | FR2610322B1 (enExample) |
| GB (1) | GB2200910B (enExample) |
| GR (1) | GR880100042A (enExample) |
| HU (1) | HU204047B (enExample) |
| IE (1) | IE61989B1 (enExample) |
| IL (1) | IL85252A (enExample) |
| IT (1) | IT1219827B (enExample) |
| LU (1) | LU87122A1 (enExample) |
| MY (1) | MY102415A (enExample) |
| NL (1) | NL8800099A (enExample) |
| NZ (1) | NZ223359A (enExample) |
| PH (1) | PH24837A (enExample) |
| PT (1) | PT86666B (enExample) |
| SE (1) | SE466150B (enExample) |
| ZA (1) | ZA88665B (enExample) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4882343A (en) * | 1987-08-28 | 1989-11-21 | G. D. Searle & Co. | Biarylalkylimidazole derivatives as anti-depressants |
| US5861431A (en) * | 1995-06-07 | 1999-01-19 | Iotek, Inc. | Incontinence treatment |
| BR112020009361A2 (pt) | 2017-11-17 | 2020-10-13 | Cellix Bio Private Limited | composto de fórmula i, composição farmacêutica para tratar um distúrbio ocular ou complicações do mesmo, método de síntese de composto, método de tratamento de um distúrbio ocular ou complicações do mesmo em um indivíduo que precisa do mesmo e uso de um composto |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2457047A (en) * | 1946-02-13 | 1948-12-21 | Monsanto Chemicals | 2-(2'-thenyl)-4, 5-dihydroimidazoles and process for making the same |
| GB1601310A (en) * | 1978-05-23 | 1981-10-28 | Lilly Industries Ltd | Aryl hydantoins |
| JPS56131579A (en) * | 1980-03-17 | 1981-10-15 | Kissei Pharmaceut Co Ltd | Novel 1-substituted imidazole derivative |
| JPS58150566A (ja) * | 1982-03-03 | 1983-09-07 | Yoshitomi Pharmaceut Ind Ltd | 新規イミダゾ−ル誘導体 |
| DE3228266A1 (de) * | 1982-07-29 | 1984-02-02 | A. Nattermann & Cie GmbH, 5000 Köln | Imidazolylalkylthiophene, verfahren zu ihrer herstellung und diese enthaltende pharmazeutische praeparate |
| DE3329028A1 (de) * | 1983-08-11 | 1985-02-28 | Cassella Ag, 6000 Frankfurt | Substituierte (2-amino-2-imidazolin-1-yl)-essigsaeurederivate, verfahren zu ihrer herstellung, ihre verwendung und sie enthaltende pharmazeutische zubereitungen |
-
1988
- 1988-01-18 NL NL8800099A patent/NL8800099A/nl not_active Application Discontinuation
- 1988-01-18 HU HU88177A patent/HU204047B/hu not_active IP Right Cessation
- 1988-01-26 BE BE8800091A patent/BE1001005A3/fr not_active IP Right Cessation
- 1988-01-27 FR FR888801019A patent/FR2610322B1/fr not_active Expired - Lifetime
- 1988-01-27 GB GB8801804A patent/GB2200910B/en not_active Expired - Lifetime
- 1988-01-28 CH CH307/88A patent/CH675721A5/de not_active IP Right Cessation
- 1988-01-28 CA CA000557576A patent/CA1327805C/en not_active Expired - Fee Related
- 1988-01-28 LU LU87122A patent/LU87122A1/fr unknown
- 1988-01-29 IE IE24488A patent/IE61989B1/en not_active IP Right Cessation
- 1988-01-29 ES ES8800263A patent/ES2008421A6/es not_active Expired
- 1988-01-29 IT IT47578/88A patent/IT1219827B/it active
- 1988-01-29 MY MYPI88000081A patent/MY102415A/en unknown
- 1988-01-29 AT AT0018288A patent/AT395852B/de not_active IP Right Cessation
- 1988-01-29 DK DK046288A patent/DK46288A/da not_active Application Discontinuation
- 1988-01-29 GR GR880100042A patent/GR880100042A/el unknown
- 1988-01-29 AU AU10960/88A patent/AU607966B2/en not_active Ceased
- 1988-01-29 SE SE8800293A patent/SE466150B/sv not_active IP Right Cessation
- 1988-01-29 JP JP63021136A patent/JPS63201185A/ja active Pending
- 1988-01-29 ZA ZA88665A patent/ZA88665B/xx unknown
- 1988-01-29 FI FI880430A patent/FI90080C/fi not_active IP Right Cessation
- 1988-01-29 IL IL85252A patent/IL85252A/xx not_active IP Right Cessation
- 1988-01-29 PT PT86666A patent/PT86666B/pt not_active IP Right Cessation
- 1988-01-29 NZ NZ223359A patent/NZ223359A/en unknown
- 1988-01-29 PH PH36423A patent/PH24837A/en unknown
- 1988-01-29 US US07/149,812 patent/US4835174A/en not_active Expired - Fee Related
- 1988-01-30 KR KR1019880000895A patent/KR880009013A/ko not_active Ceased
-
1991
- 1991-12-27 CS CS914112A patent/CS411291A3/cs unknown
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| BV | The patent application has lapsed |